Ayahuasca and its major component harmine promote antinociceptive effects in mouse models of acute and chronic pain.
Pedro Santana Sales Lauria, Juliana de Medeiros Gomes, Lucas Silva Abreu, Rejane Conceição Santana, Victor Luiz Correia Nunes, Ricardo David Couto, Paulo Oliveira Colavolpe, Marcelo Sobral da Silva, Milena Botelho Pereira Soares, Cristiane Flora Villarreal
Journal of Ethnopharmacology April 6, 2024 DOI: 10.1016/j.jep.2024.117710 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ayahuasca Harmine |
| Dose | 24-3000 μL/kg |
| Duration | Single dose and daily for 14 days |
| Topics | Ayahuasca Serotonin |
| Keywords | #pain-relief analgesic Pain management Analgesia #Ayahuasca DMT #neuroscience brain chemistry Neurotransmitters Gaba Harmine Neuropathic pain |
| Citations | 10 |
| Key points | Ayahuasca produces consistent antinociceptive effects in mouse models of acute, inflammatory, and neuropathic pain without detectable toxicity, and harmine partially accounts for this effect. |
Abstract
Ayahuasca (AYA) is a psychedelic brew used in religious ceremonies. It is broadly used as a sacred medicine for treating several ailments, including pain of various origins. To investigate the antinociceptive effects of AYA and its mechanisms in preclinical models of acute and chronic pain in mice, in particular during experimental neuropathy. The antinociceptive effects of AYA administered orally were assessed in the following models of pain: formalin test, Complete Freund's Adjuvant (CFA)-induced inflammation, tail flick test, and partial sciatic nerve ligation model of neuropathic pain. Antagonism assays and Fos immunohistochemistry in the brain were performed. AYA-induced toxicity was investigated. AYA was chemically characterized. The antinociceptive effect of harmine, the major component present in AYA, was investigated. AYA (24-3000 μL/kg) dose-dependently reduced formalin-induced pain-like behaviors and CFA-induced mechanical allodynia but did not affect CFA-induced paw edema or tail flick latency. During experimental neuropathy, single treatments with AYA (24-3000 μL/kg) reduced mechanical allodynia; daily treatments once or twice a day for 14 days promoted consistent and sustained antinociception. The antinociceptive effect of AYA (600 μL/kg) was reverted by bicuculline (1 mg/kg) and methysergide (5 mg/kg), but not by naloxone (5 mg/kg), phaclofen (2 mg/kg), and rimonabant (10 mg/kg), suggesting the roles of GABAA and serotonergic receptors. AYA increased Fos expression in the ventrolateral periaqueductal gray and nucleus raphe magnus after 1 h, but not after 6 h or 14 days of daily treatments. AYA (600 μL/kg) twice a day for 14 days did not alter mice's motor function, spontaneous locomotion, body weight, food and water intake, hematological, biochemical, and histopathological parameters. Harmine (3.5 mg/kg) promoted consistent antinociception during experimental neuropathy. AYA promotes consistent antinociceptive effects in different mouse models of pain without inducing detectable toxic effects. Harmine is at least partially accountable for the antinociceptive properties of AYA.
Comparable studies
Other preclinical and animal studies on ayahuasca, most cited first.
Citations in the library
Cited by 8
- Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents Neuroscience & Biobehavioral Reviews September 20, 2024
- Psilocybin has no immediate or persistent analgesic effect in acute and chronic mouse pain models bioRxiv (Cold Spring Harbor Laboratory) July 7, 2025
- The unpaved road of ayahuasca, a psychoactive brew, as a treatment for neuropathic pain: A review of mechanistic insights and clinical prospects Brain Behavior and Immunity Integrative September 14, 2024
- Classic Psychedelics for Treating Chronic Pain: Mechanism and Clinical Translation Molecules July 27, 2026
- Psychedelic Therapies for Comorbid Major Depressive Disorder and Chronic Pain: A Review of Putative Mechanisms of Action. Pharmacology Research & Perspectives April 1, 2026
and 3 more in the library
Cites 28
- Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics Journal of Pharmacology and Experimental Therapeutics June 18, 2003
- Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers Psychopharmacology February 22, 2001
- Psychedelics as anti-inflammatory agents International Review of Psychiatry July 4, 2018
- Ayahuasca: Pharmacology, neuroscience and therapeutic potential Brain Research Bulletin March 11, 2016
- Ayahuasca Preparations and Serotonin Reuptake Inhibitors: A Potential Combination for Severe Adverse Interactions Journal of Psychoactive Drugs December 1, 1998
and 23 more in the library